The EM Core of this Program Project has two related purposes - to support instrumentation essential for the research proposed in the four projects of this grant and to facilitate application of the methods being developed in these projects to collaborative and independent efforts at Harvard Medical School (HMS), Brandeis, and elsewhere. The Core is a single entity with two locations ~ one at HMS (designated Core A) and one at Brandeis (designated Core B) ~ and members of all laboratories have access, when suitably trained, to instruments at either institution. By providing EM and computational facilities, the core allows the Pis of these projects to collaborate with each other and with groups in and outside of the HMS and Brandeis communities and to train postdoctoral fellows and students in the relevant methods. The principal component of the HMS core (Core A) is the electron microscopy facility, which houses four FEI electron microscopes: a Polara, a Tecnai F20, a Tecnai T12, and a CM 10. The Polara and two Tecnai microscopes are equipped with cryo-stages. The core supports the operation of these microscopes and necessary ancillary equipment as well as the salary of an EM technician who supports the facilities manager. The core also has a computational component that maintains and upgrades all standard EM software, including program suites such as FREALIGN, IMAGIC, and SPIDER, through a structural biology computational grid (SBGrid) established by the Center for Molecular and Cellular Dynamics at HMS.